This prospective study of genetic prediabetics including the offspring of two well-documented diabetic parents or the apparently unaffected monozygotic twin with a known diabetic twin mate moves into its ninth year. Over 500 so-called prediabetic subjects have been studied at least once, and approximately 300 are re-studied approximately 2 to 4 times a year. A variety of short-term pertubations are employed including standard oral, intravenous, cortisone-primed oral glucose tolerance tests, and tolbutamide and glucagon administration. Blood samples are obtained and analyzed for glucose, insulin, growth hormone, triglyceride, cholesterol and in selected subjects, glucagon. During the forthcoming year, special focus will be made upon repeating the standard oral glucose tolerance test in those subjects who have not had this test repeated within 12 to 18 months. Nearly 100 subjects have received two prior oral glucose tolerance tests and obtaining a third should allow for inter-test comparisons. In all types of pertubations under study, appropriate comparisons with healthy normal control subjects will be continued. Of the many hormonal and substrate measurements performed, discriminate factor analysis will be done in an attempt to look for metabolic and biochemical marker or markers that correlate highly with parental diabetes. Selected subanalyses of these various tests will be performed in groups of offspring of two diabetic parents constructed according to the degree, severity, and age of onset of diabetes in their parents. A careful analysis of the prevalence of overt and chemical diabetes in the prediabetic groups will be performed in order to elucidate any correlations between the nature of parental diabetes and the performance during glucose tolerance testing of prediabetic offspring.